LOXL3对肝癌免疫微环境、化学治疗耐药和免疫治疗预测影响的研究  

Bioinformatics analysis of the effect of LOXL3 on the immune microenvironment,chemotherapeutic resistance and immunotherapy prediction in liver cancer

作　　者：李梓铭 赵志刚[2] 余克富[2] LI Ziming;ZHAO Zhigang;YU Kefu(School of Pharmaceutical Sciences,Capital Medical University,Beijing 100069,China;Department of Pharmacy,Beijing Tiantan Hospital,Capital Medical University,Beijing 100070,China)

机构地区：[1]首都医科大学药学院,北京100069 [2]首都医科大学附属北京天坛医院药学部,北京100070

出　　处：《西部医学》2024年第7期951-956,共6页Medical Journal of West China

基　　金：首都医科大学科研培育基金项目(PYZ23117);首都医科大学附属北京天坛医院院科研基金(管理专项)(TYGL202217)。

摘　　要：目的运用生物信息学方法研究赖氨酸氧化酶3(LOXL3)基因在肝癌组织中的表达和对患者生存情况的影响,分析LOXL3基因对肝癌免疫微环境的影响,并对肝癌的化学治疗耐药和免疫治疗疗效进行预测。方法通过TCGA数据库和ICGC数据库分析LOXL3基因在肝癌细胞中的表达情况;采用GSEA富集分析LOXL3可能富集的相关通路;通过TIMER数据库和TISIDB分析肝癌患者中LOXL3基因表达情况与免疫细胞浸润的关系;通过GDSC数据库分析LOXL3基因与治疗中肝癌对化疗药物耐药的关系。并通过TIDE数据库对肝癌患者免疫治疗的疗效进行预测,使用Kaplan-Meier分析LOXL3基因对患者生存情况的影响。结果对于TCGA和ICGC数据库,两个数据库的结果均显示在肝癌组织中LOXL3的表达高于正常组织(P<0.05)。LOXL3对TGF-β、Wnt-β-Cantenin、Hypoxia和PI3K/AKT等通路有一定的激活作用。免疫细胞浸润水平发现,LOXL3在肝癌组织中的表达水平与B细胞(r=0.463,P<0.05)、CD8+T细胞(r=0.469,P<0.05)、CD4+T细胞(r=0.557,P<0.05)、巨噬细胞(r=0.71,P<0.05)、中性粒细胞(r=0.528,P<0.05)和树突状细胞(r=0.654,P<0.05)均呈一定的正相关。化疗敏感性分析表示在肝癌组织中,对于阿昔替尼、紫杉醇、顺铂、阿糖胞苷、喜树碱、长春碱等化疗药物,低表达LOXL3基因人群对其耐药。但在免疫治疗预测中,低表达LOXL3人群能从免疫治疗中有一定的获益。生存分析显示,高表达LOXL3的患者预后较差。结论LOXL3在肝癌组织中高表达,能激活免疫相关通路,对一些化疗药物敏感,同时免疫治疗能获益,因此可作为肝癌新型分子标志物。Objective To investigate the expression of LOXL3 gene in liver cancer tissue and its impact on patient survival using bioinformatics methods,analyze the effect of LOXL3 gene on the immune microenvironment of liver cancer,and predict the chemoresistance and immunotherapy efficacy of liver cancer.Methods The expression of LOXL3 gene in liver cancer cells was analyzed using The Cancer Genome Atlas(TCGA)and International Cancer Genome Consortium(ICGC)databases.Gene Set Enrichment Analysis(GSEA)was used to analyze the possible enriched pathways of LOXL3.The relationship between LOXL3 gene expression in liver cancer patients and immune cell infiltration was analyzed using the Tumor Immune Estimation Resource(TIMER)database and TISIDB.The relationship between LOXL3 gene and chemoresistance in liver cancer was analyzed using the Genomics of Drug Sensitivity in Cancer(GDSC)database.The immunotherapy efficacy of liver cancer patients was predicted using the Tumor Immune Dysfunction and Exclusion(TIDE)database,and the impact of LOXL3 gene on patient survival was analyzed using Kaplan-Meier analysis.Results The results of both TCGA and ICGC databases showed that the expression of LOXL3 was higher in liver cancer tissue than in normal tissue,and the difference was statistically significant.LOXL3 had certain activation effects on pathways such as TGF-β,Wnt-β-Cantenin,Hypoxia,and PI3K/AKT.The level of immune cell infiltration revealed that the expression level of LOXL3 in liver cancer tissue was positively correlated with B cells(r=0.463,P<0.05),CD8+T cells(r=0.469,P<0.05),CD4+T cells(r=0.557,P<0.05),macrophages(r=0.71,P<0.05),neutrophils(r=0.528,P<0.05),and dendritic cells(r=0.654,P<0.05).Chemotherapy sensitivity analysis indicated that the low expression of LOXL3 gene in liver cancer tissue was resistant to chemotherapeutic drugs such as axitinib,paclitaxel,cisplatin,gemcitabine,vincristine,and vinblastine.However,in immunotherapy prediction,the low expression of LOXL3 in liver cancer patients could benefit from immunothera

关 键 词：肝癌 LOXL3 免疫微环境 化疗敏感性 免疫治疗 

分 类 号：R735[医药卫生—肿瘤]